TY - JOUR
T1 - Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
AU - García-Marín, Luis M.
AU - Campos, Adrian I.
AU - Diaz-Torres, Santiago
AU - Rabinowitz, Jill A.
AU - Ceja, Zuriel
AU - Mitchell, Brittany L.
AU - Grasby, Katrina L.
AU - Thorp, Jackson G.
AU - Agartz, Ingrid
AU - Alhusaini, Saud
AU - Ames, David
AU - Amouyel, Philippe
AU - Andreassen, Ole A.
AU - Arfanakis, Konstantinos
AU - Arias-Vasquez, Alejandro
AU - Armstrong, Nicola J.
AU - Athanasiu, Lavinia
AU - Bastin, Mark E.
AU - Beiser, Alexa S.
AU - Bennett, David A.
AU - Bis, Joshua C.
AU - Boks, Marco P.M.
AU - Boomsma, Dorret I.
AU - Brodaty, Henry
AU - Brouwer, Rachel M.
AU - Buitelaar, Jan K.
AU - Burkhardt, Ralph
AU - Cahn, Wiepke
AU - Calhoun, Vince D.
AU - Carmichael, Owen T.
AU - Chakravarty, Mallar
AU - Chen, Qiang
AU - Ching, Christopher R.K.
AU - Cichon, Sven
AU - Crespo-Facorro, Benedicto
AU - Crivello, Fabrice
AU - Dale, Anders M.
AU - Smith, George Davey
AU - de Geus, Eco J.C.
AU - De Jager, Philip L.
AU - de Zubicaray, Greig I.
AU - Debette, Stéphanie
AU - DeCarli, Charles
AU - Groenewold, Nynke A.
AU - Hoekstra, Pieter J.
AU - Niessen, Wiro J.
AU - Penninx, Brenda W.J.H.
AU - Schmaal, Lianne
AU - van der Meer, Dennis
AU - Medland, Sarah E
AU - Rentería, Miguel E
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/11
Y1 - 2024/11
N2 - Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.
AB - Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.
UR - http://www.scopus.com/inward/record.url?scp=85206981232&partnerID=8YFLogxK
U2 - 10.1038/s41588-024-01951-z
DO - 10.1038/s41588-024-01951-z
M3 - Article
C2 - 39433889
AN - SCOPUS:85206981232
SN - 1061-4036
VL - 56
SP - 2333
EP - 2344
JO - Nature genetics
JF - Nature genetics
IS - 11
ER -